细胞外基质金属蛋白酶诱导因子（EMMPRIN）的表达参与人肾移植间质纤维化和肾小管萎缩的发展过程。

EMMPRIN expression is involved in the development of interstitial fibrosis and tubular atrophy in human kidney allografts.

作者信息

Kemmner Stephan, Schulte Christian, von Weyhern Claus Hann, Schmidt Roland, Baumann Marcus, Heemann Uwe, Renders Lutz, Schmaderer Christoph

机构信息

Department of Nephrology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.

Department of Pathology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.

出版信息

Clin Transplant. 2016 Mar;30(3):218-25. doi: 10.1111/ctr.12677. Epub 2016 Jan 30.

DOI:10.1111/ctr.12677

PMID:26659824

Abstract

BACKGROUND

Matrix metalloproteinases (MMP) are involved in the development of interstitial fibrosis and tubular atrophy (IF/TA) in renal disease. The synthesis of MMP is activated by the extracellular matrix metalloproteinases inducer protein (EMMPRIN). To analyze the role of EMMPRIN in IF/TA, we retrospectively detected EMMPRIN expression in specimens of human renal allografts with various levels of IF/TA.

METHODS

Immunohistochemistry was performed to detect EMMPRIN expression. In a retrospective analysis, a total cohort of 50 specimens were divided according to BANFF-classification into four subgroups (0-3): no, mild (≤ 25%), moderate (26-50%), or severe (>50%) IF/TA. Among other parameters, renal function was analyzed and compared to EMMPRIN expression.

RESULTS

In 24 of 38 biopsies, we detected positive EMMPRIN staining. All nephrectomy (n = 12) samples were negative for EMMPRIN. Positive staining in the biopsy samples was detectable on the basolateral side of tubular epithelial cells. EMMPRIN staining was negatively correlated with IF/TA (p < 0.001). We found significant differences between the mean EMMPRIN expression in IF/TA groups 0 and 3 (p = 0.021) and groups 1 and 3 (p = 0.004). Furthermore, we found significant correlations between EMMPRIN staining and renal function.

CONCLUSION

Our data suggest that EMMPRIN is involved in the pathophysiology of IF/TA.

摘要

背景

基质金属蛋白酶（MMP）参与肾脏疾病中肾小管间质纤维化和肾小管萎缩（IF/TA）的发展。MMP的合成由细胞外基质金属蛋白酶诱导蛋白（EMMPRIN）激活。为分析EMMPRIN在IF/TA中的作用，我们回顾性检测了不同IF/TA水平的人肾移植标本中EMMPRIN的表达。

方法

采用免疫组织化学法检测EMMPRIN的表达。在一项回顾性分析中，根据班夫分类法将总共50个标本分为四个亚组（0 - 3级）：无、轻度（≤25%）、中度（26 - 50%）或重度（>50%）IF/TA。除其他参数外，分析肾功能并与EMMPRIN表达进行比较。

结果

在38例活检标本中的24例中，我们检测到EMMPRIN染色呈阳性。所有肾切除标本（n = 12）的EMMPRIN均为阴性。活检标本中的阳性染色可在肾小管上皮细胞的基底外侧检测到。EMMPRIN染色与IF/TA呈负相关（p < 0.001）。我们发现IF/TA 0级和3级组（p = 0.021）以及1级和3级组（p = 0.004）的平均EMMPRIN表达之间存在显著差异。此外，我们发现EMMPRIN染色与肾功能之间存在显著相关性。